TY - JOUR
T1 - Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential
AU - Kischkel, Brenda
AU - Boniche-Alfaro, Camila
AU - Menezes, Isabela de Godoy
AU - Rossi, Suelen Andreia
AU - Angeli, Claudia Blanes
AU - de Almeida, Sandro Rogério
AU - Palmisano, Giuseppe
AU - Lopes-Bezerra, Leila
AU - Nosanchuk, Joshua D.
AU - Taborda, Carlos Pelleschi
N1 - Funding Information:
This research was funded by São Paulo Research Foundation (FAPESP) grants 2016/08730-6, 2018/26402-1, 2014/06863-3, 2018/18257-1, 2018/15549-1 and 2017/25780-0. CNPq (grant 420480/2018-8) and CAPES-Education Ministry, Brazil. CT and GP are research fellows of the CNPq.
Publisher Copyright:
Copyright © 2021 Kischkel, Boniche-Alfaro, Menezes, Rossi, Angeli, de Almeida, Palmisano, Lopes-Bezerra, Nosanchuk and Taborda.
PY - 2021/11/22
Y1 - 2021/11/22
N2 - As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map Histoplasma capsulatum epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (Mφ). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and Mφ, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-γ, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species.
AB - As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map Histoplasma capsulatum epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (Mφ). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and Mφ, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-γ, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species.
KW - dimorphic-fungi
KW - pan-fungal
KW - peptide
KW - proteomic
KW - vaccine
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U2 - 10.3389/fimmu.2021.764501
DO - 10.3389/fimmu.2021.764501
M3 - Article
C2 - 34880863
AN - SCOPUS:85120678916
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 764501
ER -